Reactions of ferric heme-containing fragments with apofragments to form ordered complexes closely resembling native cytochrome c were studied under conditions which resolve the overall process into consecutive second order and first order kinetic steps. The second order reaction step results in species exhibiting the tryptophan fluorescence quenching of native cytochrome c and possibly containing substantial helical structure, but lacking coordination of methionine 80 to the heme iron. Methionine ligation and a substantial increase in the oxidation-reduction potentials are achieved in the first order phase of the reaction. The first order kinetic steps appear to involve a substantial decrease in the conformational energy with relatively small changes in the ordering of the polypeptide chains. The complementation reactions of ferrous heme-containing fragments with apofragments were also studied. In the presence of imidazole, second order rate constants virtually identical with these for ferric heme fragments were obtained. In the absence of imidazole, the complementation reactions of ferrous heme fragments are much faster than those of the corresponding ferric heme fragments, reflecting the effect of the valence of the heme iron on the folding pathway in the absence of imidazole.